Although the importance of products of the prostaglandin (PG) G/H synthase (S) enzymes -[unreadable] colloquially known as cyclooxygenases (COXs) - in cardiovascular homeostasis has attracted much[unreadable] attention, little is known about the role of PGD2. This is the most abundant COX product of mast cells,but is[unreadable] also made by platelets, macrophages, endothelial and vascular smooth muscle cells (VSMCs) and[unreadable] lymphocytes. Although PGD2 can inhibit platelet function in vitro and has been suggested to contribute to[unreadable] resolution of inflammation, almost nothing is known of its importance in cardiovascular biology in vivo. One J[unreadable] ring metabolite, 15-deoxy delta(12,14)PGJ2 at high concentrations ligates PPARgamma ,inhibits IKKbeta and induces[unreadable] oapoptosis. PGD2 activates two receptors, DP1 and DP2 and endogenous concentrations of 15-deoxy delta(12,14)[unreadable] PGJ2 also activate the DP2. Both DPs are expressed in murine VSMCs and DP1 antagonism limits[unreadable] development of abdominal aortic aneurysmal (AAA). These translational studies are designed to investigate[unreadable] the role of PGD2 and related compounds in the response to vascular injury, combining genetic and[unreadable] pharmacological approaches in diverse models of injury in mice (wire injury, flow dependent remodeling,[unreadable] AAA, atherogenesis and the response to IPS) and humans (angioplasty, acute coronary syndrome and LPS[unreadable] administration). We shall utilize novel targeted lipidomic approaches to elucidate the role of COXs and PGD[unreadable] synthases in biosynthesis of these compounds under physiological conditions and in models of vascular[unreadable] injury in humans and in mice. Furthermore, we will elucidate the mechanism of niacin stimulated[unreadable] biosynthesis of PGD2 and the relevance of these products to the vascular response to niacin in humans.[unreadable] These studies will clarify the role of PGD2 and the diverse PCs formed from it in vascular biology, just as[unreadable] drugs targeting the PGDS enzymes and the DPs are being considered for clinical development. They[unreadable] elucidate the human pharmacology of niacin in conjunction with Project by Radar and integrate closely with study of the impact of variants in genes of this biosynthetic/response pathway in the phenotypes evoked in humans and described in Project by Reilly. It draws heavily on the lipidomic and proteomic resources of the Biomarker Core and utilizes the[unreadable] diverse models available through the Animal Model Core.